It has long been known that the beneficial effects of opiate analgesia are tempered by rapidly developing tolerance to and dependence on the narcotic. Nevertheless, there are several potential mechanisms to circumvent opiate addition and maintain potent analgesia. It is now known that mu, delta, and kappa opioid receptor types can all mediate the analgesic response. Although mu receptor activation has the potential of addiction liability, recently it has been shown that some opioid compounds with lower efficacy at the mu receptor can maintain potent analgesic activity while possessing a much reduced addiction liability. Furthermore, low efficacy in agonists have been shown to have potential for the treatment of drug abuse. Using the mu receptor-containing neuroblastonia cell line SH-SY5Y we can measure receptor binding affinity and a biochemical measure of receptor activity (inhibition of cAMP accumulation) under identical conditions. Relative efficacies can be calculated based upon the definition that relative efficacy equals relative activity at equal receptor occupancy. This system can provide a simple in vitro screen for opiates with low abuse potential. General information about receptor-effector coupling for mu opioid receptors will also be gained by treatment of cells with beta-CNA to inactivate the receptors, pertussis toxin to inactivate the G-protein G-i, and high potassium or veratridine to depolarize the cell. Another mechanism to circumvent opiate addiction is the use of another receptor type. Although it has been shown that delta receptors can mediate analgesia, addiction through this receptor has not been well characterized. In addition, there has been recent interest in the characterization of delta subtypes and their molecular interactions with mu receptors. Delta receptors may have a modulatory role in opiate analgesia. Because SH-SY5Y cells contain both mu and delta receptors, the delta receptor subtype can be characterized, and interactions between mu and delta receptors can be studied in single cells. Studies of mu efficacies, delta receptors, and mu-delta interactions should lead to a better understanding of opioid actions and aid in the development of analgesics with low abuse potential.